Issue 41, 2017

Exploring the origins of selectivity in soluble epoxide hydrolase from Bacillus megaterium

Abstract

Epoxide hydrolase (EH) enzymes catalyze the hydration of racemic epoxides to yield their corresponding vicinal diols. These enzymes present different enantio- and regioselectivity depending upon either the substrate structure or the substitution pattern of the epoxide ring. In this study, we computationally investigate the Bacillus megaterium epoxide hydrolase (BmEH)-mediated hydrolysis of racemic styrene oxide (rac-SO) and its para-nitro styrene oxide (rac-p-NSO) derivative using density functional theory (DFT) and an active site cluster model consisting of 195 and 197 atoms, respectively. Full reaction mechanisms for epoxide ring opening were evaluated considering the attack at both oxirane carbons and considering two possible orientations of the substrate at the BmEH active site. Our results indicate that for both SO and p-NSO substrates the BmEH enantio- and regioselectivity is opposite to the inherent (R)-BmEH selectivity, the attack at the benzylic position (C1) of the (S)-enantiomer being the most favoured chemical outcome.

Graphical abstract: Exploring the origins of selectivity in soluble epoxide hydrolase from Bacillus megaterium

Supplementary files

Article information

Article type
Paper
Submitted
26 Jūl. 2017
Accepted
05 Okt. 2017
First published
11 Okt. 2017
This article is Open Access
Creative Commons BY-NC license

Org. Biomol. Chem., 2017,15, 8827-8835

Exploring the origins of selectivity in soluble epoxide hydrolase from Bacillus megaterium

E. Serrano-Hervás, M. Garcia-Borràs and S. Osuna, Org. Biomol. Chem., 2017, 15, 8827 DOI: 10.1039/C7OB01847A

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